基于“久病及肾”和孟德尔随机化研究探讨虚弱与肾功能的因果关系
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四川省科技计划重点研发项目(2021YFS0058); 四川省南充市科技局市校合作重大项目(19SXHZ0439); 四川省南充市名老中医青年项目(YAZX22-QN-01); 川北医学院校级科研发展基金项目(CBY21-QA21);


Explore the causal relationship between frailty and kidney function based on chronic kidney disease theory and mendelian randomization
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    摘要:

    目的:通过孟德尔随机化探究虚弱和肾功能之间的因果关系。方法:从大样本全基因关联研究数据库(GWAS)中筛选出与虚弱相关的单核苷酸多态性(SNP)作为工具变量,采用逆方差加权法(IVW)、MR-Egger、加权中位数三种分析方法进行孟德尔随机分析,以β值和95%CI评价虚弱与肾功能之间的因果关系。同时,为确保研究结果的可靠性和稳健性,利用Cochran's Q检验、MR-Egger、MR-PRESSO和留一法分析进行异质性检验、敏感性分析和多效性检验。结果:IVW估计值表明,虚弱与血尿素氮之间存在负性因果关系(β=-0.030,95%CI:-0.055~-0.006,P=0.013),同样,虚弱与胱抑素C估算肾小球滤过率之间也存在负性因果关系(β=-0.045,95%CI:-0.065~-0.025,P<0.001),未发现虚弱与尿白蛋白/肌酐比值、肾功能肌酐、慢性肾病之间的因果关系。结论:本研究证实了虚弱与肾功能之间的因果关系,为中西医结合预防和治疗虚弱及肾功能损害提供参考。

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    Objective:To investigate the causal relationship between frailty and kidney function through Mendelian randomiza-tion.Methods:Single nucleotide polymorphisms(SNP)significantly associated with frailty were selected from a large genome-wide as-sociation study(GWAS)database as instrumental variables.Mendelian randomization was performed using three approaches:inverse variance weighted,MR-Egger,and weighted median.The causal link between frailty and kidney function was evaluated using β values and 95%CI.Meanwhile,to ensure the reliability and robustness of the findings,heterogeneity tests,sensitivity analysis,and pleiotropy tests were performed using Cochran's Q test,MR-Egger,MR-PRESSO,and leave-one-out analysis.Results:The IVW estimate revealed a significant negative causal relationship between frailty and blood urea nitrogen(β=-0.030,95%CI:-0.055~-0.006,P=0.013).Similarly,a negative causal relationship was found between frailty and the cystatin C-estimated glomerular filtration rate(β=-0.045,95%CI:-0.065~-0.025,P<0.001).However,no causal relationship was observed between frailty and the urinary albu-min/creatinine ratio,serum creatinine,or chronic kidney disease.Conclusion:This study confirms the causal relationship between frail-ty and kidney function,providing a reference for the prevention and treatment of frailty and kidney function impairment by integration of traditional Chinese and Western medicine.

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罗春秀;龙凤;张哲;雷枭;郭金莲;.基于“久病及肾”和孟德尔随机化研究探讨虚弱与肾功能的因果关系[J].川北医学院学报,2025,40(2):142-147.

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  • 在线发布日期: 2025-07-24
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